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Glaucoma drainage devices: a systematic literature review and current controversies.

Glaucoma drainage devices create alternate aqueous pathways by channeling aqueous from the anterior chamber through a long tube to an equatorial plate that promotes bleb formation. Glaucoma drainage devices are being used more frequently in the treatment of glaucoma that does not respond to medications or trabeculectomy operations. In certain conditions, such as neovascular glaucoma, iridio-corneal syndrome, penetrating keratoplasty with glaucoma, glaucoma following retinal detachment surgery, and so on, it is becoming the primary operation. This review provides a systematic review of the literature and outlines the current controversies involving different glaucoma drainage devices and their design, overall surgical success, and complications following glaucoma drainage device insertion.

Clinical Trials as Topic↗

The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group.

PURPOSE: In a companion paper, we determined that intraocular pressure is part of the pathogenesis of normal-tension glaucoma by analyzing the effect of a 30% intraocular pressure reduction on the subsequent course of the disease. We report an intent-to-treat analysis of the study data to determine the effectiveness of pressure reduction. METHODS: One eligible eye of 145 subjects with normal-tension glaucoma was randomized either to no treatment (control) or to a 30% intraocular pressure reduction from baseline. To be eligible for randomization, the normal-tension glaucoma eyes had to show documented progression of field defects or a new disk hemorrhage or had to have field defects that threatened fixation when first presented for the study. Survival analysis compared time to progression of all randomly assigned patients during the course of follow-up from the initial baseline at randomization. In a separate analysis, data of patients developing cataracts were censored at the time that cataract produced 2 lines of Snellen visual acuity loss. RESULTS: Visual field progression occurred at indistinguishable rates in the pressure-lowered (22/66) and the untreated control (31/79) arms of the study (P = .21). In an analysis with data censored when cataract affected visual acuity, visual field progression was significantly more common in the untreated group (21/79) compared with the treated group (8/66). An overall survival analysis showed a survival of 80% in the treated arm and of 60% in the control arm at 3 years, and 80% in the treated arm and 40% in the controls at 5 years. The Kaplan-Meier curves were significantly different (P = .0018). The analyses gave different results because of a higher incidence of cataract in the group that underwent filtration surgery. CONCLUSIONS: The favorable effect of intraocular pressure reduction on progression of visual change in normal-tension glaucoma was only found when the impact of cataracts on visual field progression, produced largely by surgery, was removed. Lowering intraocular pressure without producing cataracts is beneficial. Because not all untreated patients progressed, the natural history of normal-tension glaucoma must be considered before embarking on intraocular pressure reduction with therapy apt to exacerbate cataract formation unless normal-tension glaucoma threatens serious visual loss.

Aged↗

Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph.

OBJECTIVE: To detect and quantitate changes in optic nerve morphology after glaucoma surgery using the Heidelberg Retina Tomograph (HRT, Heidelberg Instruments, Heidelberg, Germany). DESIGN: Nonconsecutive observational case series. PARTICIPANTS AND INTERVENTION: The authors prospectively enrolled 21 adult patients undergoing incisional glaucoma surgery for progressive glaucoma damage. Quantitative analysis of the optic nerve head by scanning laser tomography and automated perimetry were performed before and after glaucoma surgery. MAIN OUTCOME MEASURES: Changes in optic nerve parameters were subjected to linear regression analysis with respect to percent of postoperative reduction of intraocular pressure (IOP), as well as with respect to age, refraction, preoperative cup:disc ratio, and change in visual field parameters. RESULTS: Seventeen patients had pre- and postoperative images suitable for analysis. Mean IOP at the time of image acquisition before surgery was 30.5+/-12 mm Hg, and after surgery 11.8+/-5.2 mm Hg (mean follow-up, 26+/-7 weeks). Eleven of 13 (85%) patients having IOP reduction of greater than 40% showed improvement in optic disc parameters. All four patients with less than 25% reduction in IOP showed worsening of most parameters. Changes in optic disc parameters were highly correlated with percent IOP reduction and with age. The parameters in which change most strongly correlated with percent change of IOP were cup area, rim area, cup:disc ratio, and mean cup depth (each, P<0.005). The age of the patient correlated highly with change in maximum cup depth (P<0.005). Refraction and clinically determined cup:disc ratio correlated poorly with changes in measured optic disc parameters. Clinical improvement in visual fields was correlated with the degree of improvement of cup:disc ratio (P = 0.025). CONCLUSION: Most patients showing a 40% lowering of IOP after glaucoma surgery show improved optic nerve morphology as measured by the HRT. The amount of improvement correlated highly with the percent reduction of IOP.

Adult↗

Modulation of wound healing after glaucoma surgery.

The healing process after glaucoma filtration is the main determinant of surgical failure and, even more important, the final intraocular pressure. The ability to fully control wound healing may ultimately give us the ability to set the intraocular pressure in the low teens for all patients undergoing glaucoma filtration surgery. The authors review the changes in how to use antimetabolites to improve safety, and many of the exciting new areas of progress, including growth factor neutralization and future molecular therapies to control wound healing.

Antimetabolites↗

Role of transforming growth factor beta in conjunctival scarring.

Glaucoma is the major cause of irreversible blindness throughout the world. Of all of the treatments that are available at present, the most effective appears to be surgery; however, excessive conjunctival scarring can lead to surgical failure. In the last decade, the introduction of the anti-metabolites mitomycin-C and 5-fluorouracil as anti-scarring treatments have greatly improved the results of glaucoma surgery, but these agents are associated with complications that can potentially result in blindness. A possible target for a more physiological approach to anti-scarring is transforming growth factor beta. This review examines the role of transforming growth factor beta in conjunctival scarring and discusses promising new ways of modifying its activity.

Animals↗

Glaucoma management in developing countries: medical, laser, and surgical options for glaucoma management in countries with limited resources.

PURPOSE OF REVIEW: Most people affected by glaucoma live in developing countries. Recent trials and reports provide sound evidence for management of glaucoma. This review extrapolates relevant articles to the developing world. RECENT FINDINGS: The predictive value of gonioscopy for progression of primary angle closure suspects (PACS) to primary angle closure (PAC) is only 22% (95% CI: 9.80-34.2). PACS are not uncommon; laser peripheral iridotomy (LPI) is neither indicated nor feasible for all. Twenty-eight and a half percent of PAC progress to primary angle closure glaucoma; the number needed to treat (NNT) for LPI to prevent progression is only 4. Laser peripheral iridoplasty controls acute angle closure glaucoma (AACG) faster than medical therapy alone. Primary lens extraction has also been suggested as treatment for AACG after control of the acute attack. A 5-year NNT for ocular hypertension (OH) of 20 is too high to allow treatment of all OH. High-risk OH and primary open angle glaucoma (POAG) have an NNT of 5 to 6 and merit treatment. Latanoprost and brimonidine are effective in lowering IOP in Asian eyes with POAG, but primary surgical therapy may be a more viable option. For cataract and coexistent glaucoma requiring filtration, trabeculectomy combined with the Blumenthal technique of cataract surgery may be as effective as trabeculectomy combined with phacoemulsification. SUMMARY: The principles of glaucoma management should be the same the world over. Considering the paucity of resources and competing opportunity costs, countries with limited resources have to extrapolate available information in a sensible and cost-effective manner.

Antihypertensive Agents↗

Risk factors for late-onset infection following glaucoma filtration surgery.

OBJECTIVE: To determine the risk factors for late-onset infection following glaucoma filtration surgery. METHODS: We performed a case-control study comparing 131 cases of late-onset infection collected from 27 surgeons at 10 centers with 500 controls matched for date of surgery and surgeon. The criterion for the presence of infection was severe anterior chamber reaction occurring later than 4 weeks after surgery. An opaque bleb and positive culture results were not required for diagnosis. Risk factors were identified by univariate and multivariate logistic regression analyses. RESULTS: Some of the risk factors that were statistically significant in the multivariate model after adjusting for age, race, and sex were (1) performance of a full-thickness rather than a guarded procedure (risk ratio [RR], 13.1; 95% confidence interval [CI], 2.12-80.9), (2) filtration surgery performed without concurrent cataract surgery (RR, 2.25; 95% CI, 1.24-4.08), (3) use of mitomycin (RR, 2.48; 95% CI, 1.06-5.83), (4) intermittent use of antibiotics after surgery (RR, 2.10; 95% CI, 1.09-4.02), and (5) continuous use of antibiotics after surgery (RR, 5.94; 95% CI, 2.09-16.9). CONCLUSIONS: Eyes undergoing full-thickness procedures or filtration surgery without cataract extraction are at increased risk for late infection. Intraoperative mitomycin and episodic or continuous antibiotic use after the postoperative period are associated with an increased risk of infection.

Aged↗

Use of the Hoskins lens in needle revision of a failed bleb after filtration surgery.

PURPOSE/METHODS: During needle revision of a failed bleb after filtration surgery, a needle is inserted through the conjunctiva and a Hoskins lens is placed on the conjunctiva over the needle. The lens blanches the conjunctival vessels and the needle tip can be pinpointed. RESULTS/CONCLUSION: This procedure has been performed in nine eyes with no major complications. Needle revision of a failed bleb can be performed efficiently with the Hoskins lens.

Filtering Surgery↗

Transconjunctival sinusotomy using the 193-nm excimer laser.

Successful surgical management of glaucoma is limited as a consequence of undesired fibroblastic response of episcleral tissues. In 10 rabbit and three human eye bank eyes, we have performed a modified sinusotomy procedure using the 193-nm excimer laser. The technique is minimally invasive. Conjunctiva is pulled over the corneoscleral limbus, and a slit-shaped (1 x 2 mm) excimer beam ablates through conjunctiva and external sclera until penetrating the outer wall of Schlemm's canal, at which time brisk egress of fluid is noted. The conjunctiva is allowed to retract, and a conjunctival bleb is formed. A single suture is used to close the conjunctival defect. Intraocular pressure in the rabbit eye was decreased from 10.0 +/- 1.8 to 4.9 +/- 1.8 mmHg immediately after surgery (p < 0.0001). Histology revealed a partial thickness, smooth-walled ablation consistent with a sinusotomy. This procedure is minimally invasive and may be useful for management of glaucoma, particularly when a substantial component of the impediment to aqueous outflow is external to the trabecular meshwork.

Animals↗

Matrix metalloproteinase inhibition modulates postoperative scarring after experimental glaucoma filtration surgery.

PURPOSE: To determine whether postoperative application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001 (ilomastat), reduces scarring after glaucoma filtration surgery. METHODS: In a randomized, prospective, masked-observer study, 40 New Zealand White rabbits underwent modified glaucoma filtration surgery. The animals were randomly allocated to receive postoperative subconjunctival injections of either phosphate-buffered saline (PBS) or 100 microM ilomastat for 10 days. The animals were killed on days 7, 14, 21, and 30. Clinical characteristics, which included bleb morphology and intraocular pressure, were recorded. Tissue sections were immunohistochemically stained for alpha smooth muscle actin (alphaSMA) and extracellular matrix components in the two groups. RESULTS: Surgical outcome was significantly prolonged in the ilomastat-treated group compared with the vehicle-treated group (P < 0.001). At day 30, all the blebs had survived except two in the ilomastat-treated group, whereas no blebs survived to day 30 with vehicle treatment (n = 11). The intraocular pressure remained significantly lower throughout the course of the experiment in the ilomastat group compared with the vehicle group (P < 0.0017). Histologically, less scar tissue was observed at the sclerostomy site with inhibition of MMP, compared with vehicle treatment. CONCLUSIONS: The data presented suggest that the healing response after surgery can be modulated by inhibiting the effects of MMPs. Inhibition of MMP significantly improved surgical outcome by reducing the amount of scar tissue produced. By targeting the actions of these proteolytic enzymes, a more controlled and physiological method of modulating scarring may be achieved.

Actins↗

2002 survey of the American Glaucoma Society: practice preferences for glaucoma surgery and antifibrotic use.

PURPOSE: To determine the preference of members of the American Glaucoma Society for the use of antifibrotic agents (mitomycin C or 5-fluorouracil or both) and glaucoma drainage devices in ten clinical settings. MATERIALS AND METHODS: Voluntary written survey of the American Glaucoma Society. RESULTS: American Glaucoma Society (AGS) members continue to report preference for mitomycin C use in ten clinical settings. The percent usage for glaucoma drainage devices has increased in poor prognosis scenarios including the following: neovascular glaucoma, previous failed trabeculectomy, previous ECCE/ICCE, previous PKP, previous scleral buckling surgery, and uveitic glaucoma. However, trabeculectomy and MMC continue to be more likely employed for surgical management. CONCLUSION: Despite the long-term complications of bleb-related infections, no statistically significant shift in preference away from MMC use or reduction in the concentration of drug delivery was observed since the 1996 survey.

Antineoplastic Agents↗

Endophthalmitis associated with the Ahmed glaucoma valve implant.

AIM: To investigate the rate, risk factors, clinical course, and treatment outcomes of endophthalmitis following glaucoma drainage implant (GDI) surgery. METHODS: A computerised relational database search was conducted to identify all patients who were implanted with Ahmed glaucoma valve (AGV) and developed endophthalmitis following surgery at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, between 1 January 1994 and 30 November 2003. Only medical records of the patients who developed endophthalmitis were retrospectively reviewed. RESULTS: 542 eyes of 505 patients who were on active follow up were included in the study. Endophthalmitis developed in nine (1.7%) eyes; the rate was five times higher in children than in adults. Delayed endophthalmitis (developed 6 weeks after surgery) occurred in eight of nine eyes. Conjunctival erosion overlying the AGV tube was present in six of nine eyes. Common organisms isolated in the vitreous included Haemophilus influenzae and Streptococcus species. Multiple regression analysis revealed that younger age and conjunctival erosion over the tube were significant risk factors associated with endophthalmitis. CONCLUSION: Endophthalmitis is a rare complication of GDI surgery that appears to be more common in children. Conjunctival dehiscence over the GDI tube seems to represent a major risk factor for endophthalmitis. Prompt surgical revision of an exposed GDI tube is highly recommended.

Adult↗

Survival analysis for success of Molteno tube implants.

AIM: To apply survival analysis in assessing the long term outcome of Molteno tube implantation and to identify risk factors for failure. METHODS: A retrospective, 10 year, consecutive case series study of 119 eyes that underwent implantation of a Molteno tube. The main outcome measures considered were intraocular pressure (IOP), visual acuity, and complications. RESULTS: A 30% or greater reduction in IOP was achieved in 68.9% of cases. However, the overall, "complete success" rate (IOP <22 mm Hg with no medications) after a mean (SD) follow up period of 43 (33) months (range 6-120) was only 33.6% despite a fall in mean (SD) IOP from 38.2 (8.2) mm Hg to 20.1 (11.0) mm Hg. The "qualified success" rate (IOP <22 mm Hg with or without medications) was 60.5%. Failure was most common in the first postoperative year but could occur after several years, the survival curve having an exponential shape. The only statistically significant risk factor for failure identified was pseudophakia, although eyes with neovascular glaucoma tended to fare poorly. Postoperative IOP tended to be lower after double plate than after single plate implantation. There was no significant difference in outcome based on age, sex, race, previous penetrating keratoplasty, or previous conjunctival surgery. CONCLUSIONS: In eyes at high risk of trabeculectomy failure, implantation of an aqueous shunt device should be considered. Pseudophakia should be considered an additional risk factor for failure. Early failure appeared relatively more common but long term follow up of all cases is recommended to ensure adequate management of late failures.

Adult↗

A Markov modelled pharmacoeconomic analysis of bimatoprost 0.03% in the treatment of glaucoma as an alternative to filtration surgery in Italy.

OBJECTIVE: Glaucoma is generally managed by decreasing the intraocular pressure (IOP) to a level believed to prevent further damage to the optic disc and loss of visual field. This may be achieved medically or surgically. The objective of this pharmacoeconomic analysis was to investigate the 4-year costs of bimatoprost 0.03% (Lumigan) eye drops as an alternative to filtration surgery (FS) for glaucoma patients on maximum tolerable medical therapy (MTMT). RESEARCH DESIGN AND METHOD: A Markov model was designed using effectiveness and resource use data from a randomized clinical trial and expert statements (Delphi panel). The RCT covered 83 patients on MTMT. The Model compared bimatoprost with FS. In the bimatoprost model arm patients began treatment with bimatoprost. If target IOP (-20%) was not reached using medical therapy the patient proceeded with FS. In the FS model arm, FS was performed after the first ophthalmologist visit. Unit costs were obtained from an Italian chart and tariffs review (healthcare sector perspective). RESULTS: The RCT showed that 74.7% of the patients delayed the need for FS by 3 months. The Markov model forecasted that 64.2% of the patients could delay the need for FS by 1 year, and forecasted 34.0% could avoid FS after 4 years. The 4-year cost per patient in the bimatoprost and FS arms was E3438 and E4194, respectively (incremental costs of E755). The major cost drivers for the bimatoprost arm were patients who needed combination therapy or FS if the target IOP was not reached. In the FS arm, the major cost drives were the initial surgery costs and pressure-lowering medications used as add-on therapy after FS. CONCLUSIONS: The analysis shows that in a 4-year perspective bimatoprost is cheaper compared to FS. In addition, the postponement of FS associated with bimatoprost may have important implications for waiting list planning.

Aged↗

Effects of postoperative mitomycin C on glaucoma filtration surgery in rabbits treated preoperatively with antiglaucoma medications.

In a rabbit model, we evaluated the effects of topically applied postoperative mitomycin C (MMC) on the success rate of glaucoma filtration surgery in animals treated preoperatively with pilocarpine hydrochloride 4% and levobunolol hydrochloride (Betagan) for 16 weeks. Full-thickness filtration surgery was performed with a single 5-minute intraoperative exposure to a sponge soaked with 0.4 mg/mL MMC of one eye in nine rabbits in one group (group A) and to both eyes in 13 rabbits in a second group (group B). In addition, one eye of each rabbit in group B received a daily drop of 0.4 mg/mL MMC for 13 days after the operation. All of the eyes were then followed for 80 days. The intraoperatively applied MMC enhanced the success rate of the filtration surgery in the group A eyes. However, the eyes that also received postoperative drops of MMC (group B) had longer periods of reduced intraocular pressure (IOP) (P [chi-squared = 5.94] < .025), fewer bleb failures (P [chi-squared = 8.09] < .005), and more complications than the eyes that received only intraoperative MMC.

Administration, Topical↗

No-stitch combined glaucoma cataract-surgery.

A new method of small incision cataract surgery is presented which allows sutureless wound closure with a fistulating aperature for regulating IOP. After in-the-bag pcIOL implantation, a triangular opening is made into the posterior scleral valve and combined with a peripheral iridectomy. Sufficient regularization of the IOP and good visual results could be observed in the majority of all 61 eyes operated on using this method.

Aged↗

Novel antisense oligonucleotides targeting TGF-beta inhibit in vivo scarring and improve surgical outcome.

The scarring response is an important factor in many diseases throughout the body. In addition, it is a major problem in influencing results of surgery. In the eye, for example, post-operative scarring can determine the outcome of surgery. This is particularly the case in the blinding disease glaucoma, where several anti-scarring regimens are currently used to improve glaucoma surgery results, but are of limited use clinically because of severe complications. We have recently identified transforming growth factor-beta (TGF-beta) as a target for post-operative anti-scarring therapy in glaucoma, and now report the first study of novel second-generation antisense phosphorothioate oligonucleotides against TGF-beta in vivo. Single applications of a TGF-beta OGN at the time of surgery in two different animal models closely related to the surgical procedure performed in glaucoma patients, significantly reduced post-operative scarring (P<0.05) and improved surgical outcome. Our findings suggest that TGF-beta antisense oligonucleotides have potential as a new therapy for reducing post-surgical scarring. Its long-lasting effects after only a single administration at the time of surgery make it particularly attractive clinically. Furthermore, although we have shown this agent to be useful in the eye, it could have widespread applications anywhere in the body where the wound-healing response requires modulation.

Amino Acid Sequence↗

Current techniques in wound healing modulation in glaucoma surgery.

The wound healing response is the single most important determinant of the final intraocular pressure after glaucoma surgery. The use of antiscarring agents, particularly the antimetabolites 5-fluorouracil and mitomycin C, have revolutionized glaucoma surgery over the past decade. This subject has become more important with the realization that simply lowering the intraocular pressure to below 21 mm Hg is inadequate, and that optimal lowering of the intraocular pressure should be achieved in all patients undergoing surgery for glaucoma. However, the antimetabolites still have many potential problems and side effects, some of which are potentially sightthreatening. This review concentrates on the recent publications in this field that have determined the current "state of the art," with a view toward optimizing results and minimizing side effects for our patients with glaucoma in this exciting and challenging area of progress.

Animals↗